KEGGlincs Workflows

Shana White

2018-10-30

##Overview of KEGGlincs

The package KEGGlincs and the functions contained within it are designed such that users can explore KEGG pathways in a more meaningful and informative manner both visually and analytically. This method of pathway analysis is approached via functions that handle the following (related) objectives:

The idea of ‘expanded’ nodes and edges should become very clear after reviewing the following example KEGGlincs workflows. Please keep in mind, the individual functions detailed in the following workflows are incorporated into the KEGG_lincs ‘master function’; these workflows are designed to provide users a with a better understanding of how this function works, how pathway topology is represented in KGML files, and how this package could be used with non-LINCS edge data (see Workflow 2).

This workflow is intended to give users insight into the ‘expansion’ of KEGG pathway mapping via manipulation of the source KGML file. The only input required is the KEGG pathway ID for your pathway of choice. The primary goal for this method of pathway re-generation is to give users insight into the complexity that underlies many KEGG pathways but is in a sense ‘hidden’, yet hard-coded, in the curated KGML files. Users can also see the exact pathway topology that is used for input in analyses such as SPIA (Signaling Pathway Impact Analysis).

#####Rendering of the png file for the p53 signaling pathway from KEGG:

#####The following commands produce ‘expanded’ node and edge sets Note that KEGG IDs are converted to gene/compound symbols; this conversion accounts for the majority of computing time behind the expand_KEGG_mappings function. For quicker map generation, users may chose to change the argument convert_KEGG_IDs to FALSE; this will result in edges being identified by pairs of accession numbers instead of symbols in the final pathway map (example at end of this workflow using KEGG_lincs master function).

Notice that the original KEGG pathway image includes visual elements such as cellular-component-demarcations and certain edges (especially those ‘connecting’ genes to other pathways) that are not rendered in Cytoscape. These are features that are either not explicitly part of the pathway topology (i.e. not nodes or edges connecting nodes) or have not been hard-coded in the KGML file. The node labels may also differ between maps (KEGGlincs labels nodes as the first ‘alias’ in the respective KGML slot as there is no corresponding ‘label’ slot).

#####Alternative: KEGG_lincs master function The steps above may be avoided if the user does not wish to generate intermediary files/objects by making use of the function KEGG_lincs as follows: